Impaired glucose tolerance (IGT) is a pre-diabetic state of dysglycemia that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years. IGT is also a risk factor for mortality. According to the criteria of the World Health Organization and the American Diabetes Association, impaired glucose tolerance is defined as two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test. A patient is said to be under the condition of IGT when he/she has an intermediately raised glucose level after 2 hours, but less than would qualify for type 2 diabetes mellitus. The fasting glucose may be either normal or mildly elevated.
Diabetes includes Type 1, Type 2 and Gestational Diabetes. Type 1 diabetes: results from the body's failure to produce insulin, and presently requires the person to inject insulin. (Also referred to as insulin-dependent diabetes mellitus, IDDM for short, and juvenile diabetes.)
Type 2 diabetes: results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. (Formerly referred to as non-insulin-dependent diabetes mellitus, NIDDM for short, and adult-onset diabetes.)
Gestational diabetes: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM.
Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.
Both type 1 and 2 are chronic conditions that usually cannot be cured.
A number of studies have been conducted to examine the effect of diet supplements, particularly high fibre supplements on control of post-prandial glucose in healthy and diabetic subjects.
Chandalia et al. in “Beneficial Effects of High Dietary Fiber Intake in Patients with Type 2 Diabetes Mellitus”, New England Journal of Medecine 2000; 342: 1392-1398, May 1, 2000, note that the American Dietary Association (ADA) recommended a moderate increase in the intake of dietary fiber to 20-35 g per day because of the cholesterol-lowering effects of soluble fibers. However, the effects of dietary fiber on glycemic control were considered (by ADA) to be inconsequential. Furthermore the expert panel of the ADA considered it difficult to achieve a high dietary intake of soluble fiber without consuming foods or supplements fortified with fiber. The above authors designed a study to determine the effects on glycemic control of increasing the intake of dietary fiber in patients with type 2 diabetes exclusively through the consumption of unfortified foods, to a level beyond that recommended by the ADA. Two diets were compared: a diet in accordance with ADA with moderate amounts of fiber (total 24 g per day, of which 8 g soluble fiber and 16 g insoluble fiber), and a diet with a high amount of fiber (total 50g per day of which 25 g soluble fiber and 25 g insoluble fiber). Both diets provided 15% of the total energy as protein. The high-fiber diet (which contained significant quantities of protein) was found to improve glycemic control, as evidenced by decreases in the mean daily preprandial and 24-hr plasma glucose concentrations, and also by lowered urinary glucose excretion.
Anderson et al. in “Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia”, The American Journal of Clinical Nutrition, October 1999 vol. 70 no 466-473 provided diabetic subjects with soluble psyllium fibers presented as a powder inside a sachet, with instructions to mix each dose of 8.7 g psyllium in 240 ml liquid and to drink the liquid 20-30 minutes before the morning and evening meals. The psyllium was provided as an orange-flavoured, sugar-free product (Metamucil; Procter and Gamble Co, Cincinnati). The control drink included an insoluble cellulose fiber, microcrystalline cellulose (Avicel, PH-101, FMC Corp, Philadelphia). For patients evaluated in the metabolic ward, psyllium showed improved metabolic control (lower blood sugar) than the control. Many changes in glycemic index during the outpatient evaluations were not significantly different.
In the introduction to the above article by Anderson et al., the authors report that early studies suggested that psyllium improved glycemic control in individuals with type 2 diabetes (e.g. Fagerberg SE, “The effects of a bulk laxative (Metamucil) on fasting blood glucose, serum lipids and other variables in constipated patients with non-insulin dependent adult diabetes”, Curr Ther Res 1982; 31:166-72) but that other studies showed no effect on glycemic control (e.g. Br J Nutr 1984; 51:371-8), and yet others found an effect only when psyllium was sprinkled onto or incorporated into a cereal meal.
With respect to the ingestion of the psyllium-based material Metamucil, it is noteworthy that the makers of Metamucil have advocated convenient and tasty recipes for consuming Metamucil fiber, and that one of these recipes has included the incorporation of Metamucil (e.g. 1 rounded teaspoon) in a milk shake (e.g. based on 8 oz of low-fat milk). The administration of Metamucil in this way as part of a disease management strategy for type 2 diabetes would provide a combination of fiber and protein, and in particular would provide a combination of fiber and whey protein. Nuttal et al. in “Effect of protein ingestion on the glucose and insulin response to a standardised oral glucose load”, Diabetes Care, 1984 September-October; 7(5): 465-70 found that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type 2 diabetic persons. The glucose meal is generally seen as representative of a high GI meal.
Gannon et al. in “The insulin and glucose responses to meals of glucose plus various proteins in type 2 diabetic subjects” Metabolism, 1988 November; 37(11): 1081-8, report prior work that shows that ingested beef protein is just as potent as glucose in stimulating a rise in insulin concentration in type 2 diabetes patients. They also report a synergistic effect (in insulin secretion) when the protein is given with glucose. A study was made of a meal consisting of 50 g glucose with 25 g protein in the form of lean beef, turkey, gelatine, egg white, cottage cheese, fish or soy. It is of interest to note that cottage cheese is a cheese curd product that is drained but not pressed, so that some whey remains. Gannon et al. found that the blood glucose response was diminished following ingestion of all meals containing protein, with the exception of egg white. These authors also found that the relative area under the insulin response curve was greatest following ingestion of the meal containing cottage cheese (360%), and was least with egg white (190%), compared with glucose alone (100%).
Bell and Shabert in U.S. Pat. No. 6,365,176 (filed Sep. 18, 2000) describe a nutritional supplement to be incorporated into the diet of a type 2 diabetic or an individual having lipodystrophy. The supplement provides food-grade ingredients to improve the management of blood glucose and blood lipid levels. The supplement comprises a low GI carbohydrate and a protein, and the carbohydrate preferably includes a fiber which may be psyllium. The protein is preferably selected from the group consisting of whey, casein, soy, milk, egg and combinations thereof claim 25 is to a supplement containing from about 1 to about 10 grams protein, and from about 0.5 to about 11 grams psyllium fiber. Claim 32 is to a method of providing an individual with nutritional supplementation that aids in the management of blood glucose levels, comprising administering to an individual in need thereof the nutritional supplement, in an amount sufficient to measure blood glucose levels. Cashmere and Besozzi in U.S. Pat. No. 4,921,877 (filed 16 Dec. 1987) describe a nutritional formula containing a unique fiber-containing carbohydrate blend and protein. The use of the formula is for the dietary management of patients with glucose intolerance. The protein source may be casein, whey or soy protein.
In Stevens et al., “Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetics”, Diabetes Care, 2009 September; 32 (9):1600-2, Epub 2009 Jun. 18 describes an experiment where subjects ingested 350 ml of beef-flavoured soup containing 55 g whey protein 30 minutes before a mashed potato meal. The postprandial glycemic peak was significantly lower than in the absence of a whey preload.
Larrauri et al., “Measurement of Health-Promoting Properties in Fruit Dietary Fibres: Antioxidant capacity, Fermrntability and Glucose Retardation Index”, Journal of the Science of Food and Agriculture, vol 71, Issue 4, pp 515-519 1996 discuss the glucose retardation index of a variety of fruit-derived dietary fibres. A high glucose retardation index is expected to be beneficial in terms of reduced postprandial blood sugar peaks.
Brown et al., in US application 20100056450 (filed Aug. 28, 2009) describes a method for reducing postprandial blood glucose levels, which includes administering a blend of native whey protein and viscosifying fiber to a subject in an amount and at a time prior to or concurrent with a meal, that is effective in reducing postprandial blood glucose levels. The examples in this application are based on the use of 5 g whey protein concentrate and 2 g hydroxypropylmethylcellulose in 400 ml liquid prior to or simultaneous with a standard bread meal (50 g available carbohydrate). The first claim teaches administering a blend of from 2 to 50 g whey to 0.5 to 20 g viscosifying fiber at least 5 to 90 minutes before a meal, the method effective for reducing postprandial blood glucose by at least 5% compared to the meal without preloading.
Garcia-Rodenas in US application 2006/0159770 (filed Jun. 30, 2004) teaches the use of a composition for treating, preventing and/or improving metabolic dysfunctions associated with type 2 diabetes and insulin resistance, said composition comprising intact whey protein. Garcia-Rodenas notes that US application 2003/0004095 teaches that milk protein hydrolysates can be used to improve glucose metabolism or control glycemic response in diabetics. Garcia-Rodenas teaches that the intact whey protein can be provided during, after or before a standard meal comprising carbohydrates.
Blackburn et al. in “Does guar gum improve post-prandial hyperglycaemia in humans by reducing small intestinal contact area?” British Journal of Nutrition 1984 September; 52(2): 197-204 explores the mechanism whereby viscous polysaccharides such as guar gum lower post-prandial blood glucose in humans.
Edwards et al., in “Viscosity of food gums determined in vitro related to their hypoglycaemic actions” Am J Clin Nutr 1987; 46: 72-7 note that gums which have the highest viscosity at equivalent concentrations and shear rates are not correspondingly efficient in lowering postprandial blood glucose in human subjects, when incorporated in a drink containing 50 g glucose. The drink volume was 250 mls, and the viscous solutions were presented as 1% (by weight) solutions of food gum in water.
It has been reported the consumption of guar gum in conjunction with a meal may be beneficial in reducing the blood sugar elevations caused by the meal. However powder-based drinks which contain high levels of guar and which are reconstituted before consumption may be rejected by patients on the basis of poor (“gluggy”) mouth-feel. Furthermore, typical variations in the reconstitution process (e.g. shape of the drink vessel, shape of the stirring implement, variable stirring actions and stirring times) can lead to significant changes in mouth-feel and homogeneity which reduces consumer confidence in the reliability of the product, and makes the conduct of reliable clinical trials problematic.
Work by the current authors has shown that the consumption of water or water-based drinks after the ingestion of a guar drink/meal combination can adversely influence the blood sugar response to the meal. The delivery of guar gum in tablet form with a meal can also lead to variable gum dissolution kinetics as the gum is influenced by food components in the meal. The volume of water associated with the guar gum in the guar drink can also change the efficacy of the guar gum treatment.
It has also been shown that the consumption of soluble proteins (350 mls of beef-flavoured soup) as a liquid pre-load 30 minutes prior to a meal can reduce the blood sugar rise in type 2 diabetes patients associated with the meal. This type of effect has also been found when the meal is taken in conjunction with a broth containing soluble protein. However 350 mls is a high drink volume, and a precise teaching on a practical, uniformly effective drink for people with diabetes or pre-diabetes (such as impaired glucose tolerance=IGT) has not been provided.
The use of drinks containing both soluble proteins and viscosifying agents (with or before a meal) has also been shown to decrease blood sugar rises from the meal in healthy people (US 20100056450). In this patent application a typical individual dose of soluble protein was whey as WPC (5 g), and a typical viscosifying agent was hydroxypropylmethylcelluose (2 g). There was no investigation of effectiveness on patients with diabetes or pre-diabetes—rather an assumption was made that an effective blood sugar reduction in healthy people would automatically translate to an effective blood sugar reduction in people with diabetes or pre-diabetes. There was also no investigation of the effect of these drinks on patients on medication for the treatment of diabetes or pre-diabetes.
It is important to note that that in many type 2 diabetes patients, the blood sugar response to a meal is much more pronounced (e.g. rising to 11 millimoles/liter rather than rising to 7 mMoles/liter) and occurs over a significantly longer time period (e.g. 4 hours rather than 45 minutes) compared with a healthy subject. The assumption that a functional drink that has good efficacy for healthy subjects will also have good efficacy for diabetic or pre-diabetic subjects is thus highly questionable.
It is known that the consumption of medicines in conjunction with gel-forming fibre can slow down the kinetics of action of the medication, leading to a diminution in the efficacy of the medication. Given that many diabetics will rely on medication such as metformin, sulfonylureas or enzyme inhibitors to control their condition, and given also that most diabetic medications are recommended to be consumed at mealtimes, the use of a gel-forming fibre in a functional drink to be taken with meals may be problematic for diabetics on medication.
There is a need for improved supplements and functional foods which control post prandial glucose profile to assist in controlling the progression of IGT to diabetes and the progression in severity of diabetes from drug therapy to combination therapy and the reliance on insulin. Such management offers the potential to reduce the complications and mortality associated with diabetes and associated diseases and reduce the significant cost to public health of these diseases.
The discussion of documents, acts, materials, devices, articles and the like is included in this specification solely for the purpose of providing a context for the present invention. It is not suggested or represented that any or all of these matters formed part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.